INDIANAPOLIS, October 25, 2011 /PRNewswire/ --Eli Lilly and
Company announces withdrawal of its Xigris(R) [drotrecogin alfa
(activated)] product in all markets following results of the
PROWESS-SHOCK study, which showed the study did not meet the
primary endpoint of a statistically significant reduction in 28-day
all-cause mortality in patients with septic shock. The company is
working with regulatory agencies on this withdrawal, and is in the
process of notifying health care professionals and clinical trial
investigators.

"While there were no new safety findings, the study failed to
demonstrate that Xigris improved patient survival and thus calls
into question the benefit-risk profile of Xigris and its continued
use," said Timothy Garnett, M.D., Lilly's Senior Vice President and
Chief Medical Officer. "Patients currently receiving treatment with
Xigris should have treatment discontinued, and Xigris treatment
should not be initiated for new patients."

"We believe the original Xigris approval was appropriate and
these recent results were quite unexpected," Garnett added. "A
contributing factor to these study results could be advances in the
standard of care for treating severe sepsis over the past 10
years."

Xigris was approved in the United States by the Food and Drug
Administration (FDA) in November 2001, and was licensed in the
European Union in 2002. The PROWESS-SHOCK study was initiated in
March of 2008 as a condition for continued market authorization in
Europe. Lilly committed to conduct a new placebo-controlled
clinical trial to help refine appropriate patient identification
for treatment with Xigris and to confirm the benefit-risk profile
of the product.

BioCritica, Inc. has sales and marketing rights for Xigris in
the United States and Puerto Rico, and Lilly sells and markets
Xigris in other countries.

Patients, physicians, pharmacists, or other healthcare
professionals with additional questions about Xigris should contact
The Lilly Answer Center at 1-800-LillyRx or visit
www.Lilly.com.

About Severe Sepsis

Sepsis is a common and deadly disease(1). Severe sepsis can
develop as a complication after common illnesses such as pneumonia
and bacterial infections, and is characterized by an overwhelming
systemic response to infection which can rapidly lead to organ
failure and ultimately death.

About Xigris

Xigris (drotrecogin alfa [activated]) is a recombinant form of
human Activated Protein C. It is administered by intravenous
infusion. Based on the results of the PROWESS study the U.S. Food
and Drug Administration approved Xigris in November 2001 for the
reduction of mortality in adult patients with severe sepsis who
have a high risk of death (e.g., as determined by APACHE II).
Xigris is not indicated in adult patients with severe sepsis and a
lower risk of death (e.g., APACHE II score <25). Xigris is not
indicated in pediatric patients. In 2002, the EMA licensed Xigris
for the treatment of adult patients with severe sepsis with
multiple organ failure when added to best standard care.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Xigris increases the risk of bleeding. Xigris is contraindicated
in the following clinical situations where bleeding could lead to
significant morbidity or death:

- Active internal bleeding

- Recent (within 3 months) hemorrhagic stroke

- Recent (within 2 months) intracranial or intraspinal surgery,
or

severe head trauma

- Trauma with an increased risk of life-threatening bleeding

- Presence of an epidural catheter

- Intracranial neoplasm or mass lesion or evidence of
cerebral

herniation

WARNINGS and PRECAUTIONS

Bleeding is the most common serious adverse effect associated
with Xigris therapy. Each patient being considered for therapy with
Xigris should be carefully evaluated and anticipated benefits
weighed against potential risks associated with therapy.

Certain conditions, many of which led to exclusion from the
Phase 3 trial (PROWESS), are likely to increase the risk of
bleeding with Xigris therapy. Therefore, for patients with severe
sepsis who have one or more of the following conditions, the
increased risk of bleeding should be carefully considered when
deciding whether to use Xigris therapy:

- Concurrent therapeutic dosing of heparin to treat an
active

thrombotic or embolic event

- Platelet count <30,000 x 10(6)/L, even if the platelet
count is

increased after transfusions

- Prothrombin time-INR >3.0

- Recent (within 6 weeks) gastrointestinal bleeding

- Recent administration (within 3 days) of thrombolytic
therapy

- Recent administration (within 7 days) of oral anticoagulants
or

glycoprotein IIb/IIIa inhibitors

- Recent administration (within 7 days) of aspirin >650 mg
per day

or other platelet inhibitors

- Recent (within 3 months) ischemic stroke

- Intracranial arteriovenous malformation or aneurysm

- Known bleeding diathesis

- Chronic severe hepatic disease

- Any other condition in which bleeding constitutes a
significant

hazard or would be particularly difficult to manage because of
its

location

Should clinically important bleeding occur, immediately stop the
infusion of Xigris. Continued use of other agents affecting the
coagulation system should be carefully assessed. Once adequate
hemostasis has been achieved, continued use of Xigris may be
reconsidered.

Mortality In Patients with Single Organ Dysfunction and Recent
Surgery

Among the small number of patients in PROWESS, with single organ
dysfunction and recent surgery (surgery within 30 days prior to
study treatment), all-cause mortality was numerically higher in the
Xigris group (28 day: 10/49; in hospital: 14/48) compared with the
placebo group (28 day: 8/49; in hospital: 8/47).

In an analysis of the subset of patients with single organ
dysfunction and recent surgery from the ADDRESS study, which
enrolled septic patients not at high risk of death, all cause
mortality was also higher in the Xigris group (28 day: 67/323; in
hospital: 76/325) compared with the placebo group (28 day: 44/313;
in hospital: 62/314). Single organ dysfunction patients with recent
surgery may not be at high risk of death irrespective of APACHE II
score. Therefore, these patients may not be among the indicated
population.

Patients on Prophylactic Heparin when Xigris is Initiated

Clinicians should consider continuing heparin for venous
thromboembolism (VTE) prophylaxis when initiating Xigris, unless
discontinuation is medically necessary. In a randomized study of
prophylactic heparin versus placebo in 1935 adult severe sepsis
patients treated with Xigris, mortality and the rate of serious
adverse events were increased in the subgroup of 434 patients whose
heparin was stopped on study entry by randomization to placebo plus
Xigris. This finding was based on prospectively defined exploratory
subgroup analyses; however, the explanation for the finding is
unclear. The safety of prophylactic heparin when concomitantly
administered with Xigris in adult patients with severe sepsis was
evaluated with low molecular weight heparin enoxaparin (40 mg every
24 hours) and unfractionated sodium heparin (5000 U every 12
hours), but was not evaluated with unfractionated sodium heparin
5000 U when dosed every 8 hours.

Invasive Procedures

Invasive procedures increase the risk for bleeding with Xigris.
Such procedures, including arterial and central venous punctures,
should be minimized during the Xigris infusion. Puncture of a
noncompressible site should be avoided during the infusion. Xigris
should be discontinued 2 hours prior to undergoing an invasive
surgical procedure or procedures with an inherent risk of bleeding.
Once adequate hemostasis has been achieved, Xigris may be restarted
12 hours after surgery and major invasive procedures or immediately
after uncomplicated less invasive procedures.

ADVERSE REACTIONS

Bleeding is the most commonly reported adverse reaction in
patients receiving Xigris therapy. Patients administered Xigris as
treatment for severe sepsis experience many events which are
potential sequelae of severe sepsis and may or may not be
attributable to Xigris therapy. In severe sepsis clinical trials,
there were no types of non-bleeding adverse events suggesting a
causal association with Xigris. In the PROWESS study, serious
bleeding events were observed during the 28-day study period in
3.5% of Xigris-treated and 2.0% of placebo-treated patients. The
difference in serious bleeding occurred primarily during
infusion.

The incidence of intracranial hemorrhage (ICH) during the study
period was 0.2% for Xigris treated patients and 0.1% for placebo
treated patients. ICH has been reported in patients receiving
Xigris in non-placebo controlled trials with an incidence of
approximately 1% during the infusion period. The risk of ICH may be
increased in patients with risk factors for bleeding such as severe
coagulopathy and severe thrombocytopenia.

*APACHE (Acute Physiology And Chronic Health Evaluation).

DR HCP ISI 091010

For more information, see full prescribing information at
http://pi.lilly.com/us/xigris.pdf.

About Eli Lilly and Company

Lilly, a leading innovation-driven corporation, is developing a
growing portfolio of pharmaceutical products by applying the latest
research from its own worldwide laboratories and from
collaborations with eminent scientific organizations. Headquartered
in Indianapolis, Ind., Lilly provides answers - through medicines
and information - for some of the world's most urgent medical
needs. Additional information about Lilly is available at
www.lilly.com.

This press release contains forward-looking statements about
Xigris and reflects Lilly's current beliefs. As with any
pharmaceutical product, there are substantial risks and
uncertainties in the process of development and commercialization.
For further discussion of these and other risks and uncertainties,
see Lilly's filings with the United States Securities and Exchange
Commission. Lilly undertakes no duty to update forward-looking
statements.

Xigris(R) (drotrecogin alfa [activated]) is a registered
trademark of Eli Lilly and Company

Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment.